Diabetes (diabetes mellitus) is one of very popular lifestyle-related diseases. In Japan now it is reported that six million people or more are suffering from the diabetes, and if the number of potential diabetes patients are added, there might be as many as 14 million diabetes patients. A symptom of the diabetes is characterized by continuous high concentration of blood glucose. One big problem is that the diabetes causes various other diseases (=complications) such as diabetic neuropathy, diabetic hypertonias and diabetic arteriosclerosis, in addition to diabetic blindness and urinemia.
The diabetes can be classified into two types. One is Type 1 diabetes, also called an insulin-dependent diabetes. The patient of Type 1 diabetes cannot secrete insulin because beta (β) cells in islet of Langerhans of pancreas (=islet beta cells), which are insulin producing and secreting cells, are destroyed due to autoimmunity or other reasons. Another is Type II diabetes, where secreted insulin doesn't work well. A typical patient of Type II diabetes is the person, whose insulin secretion is likely to decrease, additionally having the factor like obesity, mental stresses or shortage of physical activity.
The development of a diabetes model animal is very important, not only for the researches of the diabetes and its complications caused by the diabetes, but also for the development of new treatment and therapeutic agent for these diseases. So far some diabetes model animals are developed and used. Here, we explain typical two kinds of (Type I) diabetes model mice. One is a mouse which can be obtained by administrating the compound called streptozotocin that acts on specifically the islet beta cells, while the other is a mouse (NOD mouse) exhibiting a symptom similar to the diabetes, which can be established from a strain of mouse frequently having cataract.
Although the former mouse can be obtained by a simple procedure that is administration of the streptozotocin, there are problems in (1) efficiency and reproducibility to induce the diabetes and (2) side reaction to other organs and cells such as renal damages. The latter NOD mouse is thought to be suitable to the researches of the Type 1 diabetes because it resembles a symptom of the Type 1 diabetes. The problem of this model mouse is that (1) a long time rearing (breeding) is necessary (eight months or more rearing is necessary in order to develop the diabetes by 70-80%), and that (2) it is not predictable when it develops the diabetes, in addition to the problem that (3) there is male/female difference and this method is only applicable for the female mouse.
By the way, this inventor has developed an original method by which only a target cell group can be destroyed at a desired time, named TRECK (Toxin Receptor Mediated Cell Knockout) (“Protein, Nucleic acid, Enzyme” Vol. 43, No. 1, pp 11-24 (1998); Nature Biotechnology, Vol. 19, pp 746-750 (2001)). In fact, hepatic cells could be selectively destroyed using this method, i.e., by firstly producing a transgenic mouse with an expression unit including a diphtheria toxin receptor gene in the downstream of albumin enhancer/promoter which is a hepatic cell specific promoter, and then administrating a diphtheria toxin to this transgenic mouse (WO 98/33899; U.S. Pat. No. 6,576,813).